Over 2 million Americans suffer from senile dementia and another 4-5 million individuals over 65 years of age demonstrate moderate cognitive impairment. A prominent feature of this age-related cognitive disturbance is impaired memory. Strong evidence has accumulated during the last decade that suggest cholinergic neurons may have a major role in age-related memory disturbances. Recently, investigations in this laboratory provided the first demonstration of attenuation of an age-related short-term memory deficit in 24 mo old Fischer 344 rats for a radial 8-arm maze task. Attenuation of this memory deficit was obtained with 3,4-diaminopyridine (3,4-DAP), thereby introducing a new drug capable of attenuating age-related memory impairment. One purpose of this project is to establish a dose-response curve for the effects of 3,4-DAP on short-term memory performance by old rats in the 8-arm maze. Rats will be given 50 daily training trials in the radial 8-arm maze at which time they are at asymptote performance, and then on alternate days injected with a dose of either 3,4-DAP or saline for an additional 50 trials. A second purpose of this project is to investigate the effects of an interaction between choline dietary loading and treatment with 3,4-DAP. Male C57BL/6j mice will be maintained on choline diets from 8 mo of age to 13 mo of age, and then given various dosages of 3,4-DAP and examined for 7-day retention of the passive avoidance habit. The long-term goal of this research is development of an effective treatment for attenuation of cognitive impairment in senescent individuals.